Detoxifying antimicrobial molecular complex

ABSTRACT

The invention relates to a food additive which includes at least one clay interspersed with volatile antimicrobial agents. Such an additive can be added to the feed of certain animals, in particular poultry and ruminants, in order to act as a growth promoter and to reduce the risks of infection, as well as the risks of intoxication by mycotoxins.

The present invention relates to an additive for a veterinary feed, to acomposition containing this additive as well as to the method formanufacturing this composition and to the use of this composition as anadditive with multiple actions: growth promoter action, plus protectiveaction against parasitic diseases, plus adsorbing action of mycotoxins,plus immunostimulating and intestinal and hepatobiliary protectiveaction.

Pathologies which affect animals are generally multifactorial phenomenain which several elements are involved: bacteria, viruses, fungi,parasites, immunodeficiency, metabolism, physiology, zootechnicalenvironment, dietary deficiencies, toxins and others. The breedergenerally has various products which each treat one or two factorsalone. He is therefore forced to compose cocktails from these products.This has the consequence of risks of inadequacy of treatments by excessor by lack generating diverse losses. The most used administration routefor these treatments is the oral route by addition in the feed or in thedrink water.

Cattle feed inter alia contains antibiotics used as growth promoters andantiparasitic agents like a preventive treatment for coccidiosis orhistomoniasis and other parasitic diseases. These chemotherapeuticagents are questioned in several problems of animal health and publichealth for their toxicity, the residues which they may generate in foodproducts of animal origin and for their involvement in the emergence ofresistance to infectious agents, Cháfer-Pericás et al., Food Control 22(2011) 993-999.

It is for all these reasons that these agents were banned in severalregions of the world. IP/05/1687, Brussels, Dec. 22, 2005.

Cattle feed also contains non-negligible concentrations of mycotoxinsoriginating from mold which contaminate the cereals contained in thecattle feed. These mycotoxins have deleterious effects on animal healthand their residues in foods of animal origin are deleterious for thehealth of the consumer, Wayne and Bryden, Animal Feed Science andTechnology 173 (2012) 134-158.

In this context, the cattle feed manufacturers and the breedersconfronted with problems of delayed growth and of parasitic diseases areforced to find alternatives for replacing the antibiotics used as growthpromoters and the antiparasitic agents which have been banned asadditives in the feed. They also have to find additives for combatingthe negative effects related to the presence of mold which producemycotoxins and to the mycotoxins themselves (Placinta et al., A reviewof worldwide contamination of cereal grains and animal feed withFusarium mycotoxins, Animal Feed Science and Technology Volume 78, Issue1, Pages 21-37, 31 Mar. 1999).

In order to prevent these mycotoxins from passing into the blood stream,several means are used. The most used means is the use of adsorbentssuch as: hydrated sodium calcium aluminosilicate (HSCAS), activatedcoal, yeast walls, phyllosilicates, cholestyramine, lactic bacteria,Phillips, Clement & Park, 1994. Approaches to reduction of aflatoxins infoods and feeds. In D. L. Eaton & J. D. Groopman, eds. The toxicology ofaflatoxins—human health, veterinary and agricultural significance, p.383, San Diego, Calif., United States, Academic Press.

Clays activated by the addition of acids and by heating are among thoseadsorbents, EP 1 333 919 B1, Use of activated layered silicates for theadsorption of mycotoxins. However, the activation processes are verycomplicated and very expensive, which has a negative repercussion on thequality and reproducibility of the capability of adsorbing mycotoxinsand makes the price of clays too expensive especially when this iscattle feed.

Another problem related to activated clays consists in the fact thatthese clays may act as chelators of vitamins and reduce the amount ofvitamins available for the animal. This may generate problems of vitamindeficiencies.

Among the alternatives used for replacing the antibiotics andantiparasitic agents, one finds essential oils and their majoritycompounds such as thymol, carvacrol, cinnamaldehyde, eugenol and others(Alleman et al., The use of essential oils in poultry feed. INRAProductions Animales, 2013, number 1; Bento et al., Essential oils andtheir use in animal feeds for monogastric animals, Veterinarni Medicina,58, 2013 (9): 449-458; Brenes and Roura Animal Feed Science andTechnology 158 (2010) 1-14).

However, these substances are volatile and therefore unstable in thefeed. This instability is at the origin of a significant loss ofessential oils during the manufacturing of the feed. This forces cattlefeed manufacturers to add large amounts of essential oils in excess sothat the feed, once it is manufactured, still contains the requiredamount of essential oils, or to use complicated and expensivestabilization methods such as micro-encapsulation (de Barros Fernandeset al., Gum arabic/starch/maltodextrin/inulin as wall materials on themicroencapsulation of rosemary essential oil, Carbohydrate Polymers 101(2014) 524-532).

This instability is also at the origin of the short period of validityof the sought actions in cattle feed after manufacture. This has anegative repercussion on the quality of the feed containing theessential oils as an additive and increases the price of the additive,which reduces it competitiveness with antibiotics and with antiparasiticagents and other alternatives.

The object of the present invention therefore consists of inventing astable composition containing compounds having an antibiotic(antibacterial) and antiparasitic activity, an anti-fungal activitycapable of inhibiting the growth of fungi secreting mycotoxins and atthe same time the capability of adsorbing mycotoxins. Another object ofthe invention consists of selecting from among substances having theactivities mentioned above, those which also have an intestinal andhepatobiliary protective and immunostimulating activity.

Thus, against pathologies which are multifactorial phenomena affectinganimal health, the invention proposes a solution with multiple actions.

The composition, object of the present invention, and intended toachieve the aforementioned goal, results from complexation byinterspersing volatile molecules such as: thymol, cresol, carvacrol,menthol, eugenol, cinnamaldehyde, having an antibacterial,antiparasitic, antifungal and intestinal, hepatobiliary protective andimmunostimulating activity with clays. The clay having at the same timethe action of a stabilizer excipient of the composition, the action ofadsorbing mycotoxins and the action of intestinal protectors.

The expression “molecular complex” refers to any composition obtained bymixing essential oils or one of their volatile compounds with any edibleclay, the molecules of which are capable of interacting with theseessential oils and their volatile compounds.

The expression “essential oils” refers to any extract obtained fromaromatic plants by one of the known extraction methods allowing them tobe extracted.

The expression “volatile compounds of the essential oils” refers to anyvolatile molecule obtained by purification from essential oils or fromanother natural source or else by identical chemical synthesis as wellas their derivatives and isomers.

The expression “edible clay” refers to any natural or synthetic mineralsubstance having a molecular structure identical with or similar to thatof edible clays commonly used in the agrifood and pharmaceutical field.

The expression “interspersed clay” refers to any situation whereinterspersing molecules come into interaction with clay molecules bybeing inserted into the interfoliar spaces of clay, this interspersionbeing expressed by an increase in the interfoliar distance.

The expression “antimicrobial activity” refers to any inhibitory ordestructive action on microbial germs of bacterial, fungal, parasitic orviral nature.

The expression “intestinal and hepatobiliary protector” refers to anyaction allowing to preserve the physical and physiological integrity ofthe intestine and to stimulate the hepatic function so as to increaseits detoxification activity.

The expression “immunostimulating” refers to any activity allowing toreinforce natural or acquired defenses of the organism.

The expression “adsorbing toxins” refers to any allowing to bind thetoxins at the intestine level in order to prevent their absorptiontowards the blood stream.

Animal husbandry is confronted with a multitude of risk factors of thezootechnical, infectious, sanitary, hygienic, immune, physiological andfeed order which promote the occurrence of pathologies which only one ofthese factors could not cause. It is for this reason that scientistsagree on the idea that the occurrence of any disease is a multifactorialphenomenon (Sjaak de Wit, Practical epidemiology of poultry disease andmultifactorial conditions, Poultry Diseases (Sixth Edition), 2008, Pages492-509).

Hence the benefit of studying the impact of each factor separately andof providing a curative or preventive remedy to each of them in order toprevent the outbreak of the disease or to attenuate the damages which itcauses. The multitude of remedies poses a problem of cost, of dosage ofeach remedy and many other problems which complicate the work of thebreeder.

In order to overcome the problem of the use of antibiotics andantiparasitic agents of chemotherapy banned by regulations and theproblem of multiple remedies, the object of the present invention istherefore a stable composition comprising a molecular complex containingnatural molecules having multiple pharmacological, antimicrobial,immunostimulating, cholagogue, carminative activities such as thymol,cresol, carvacrol, menthol, eugenol, cinnamaldehyde, or any componentcontaining them separately or mixed as well as the isomers, derivativesand mixtures thereof. These volatile molecules are bound and stabilizedby interspersion into the inferfoliar space of clays having propertiesfor adsorption of toxins, intestinal protectors, and hydratingproperties such as stevensite, bentonite, kaolinite, smectite, illite,chlorite, montmorillonite, laponite, beidellite, nontronite, saponite,sauconite, hectorite, halloysite, vermiculite, or sepiolite or theirnatural or caused interlayered mixtures.

In a particular embodiment, the composition may comprise said volatileantimicrobial agents which are antiseptic aromatic alcohols selectedfrom thymol, cresol, carvacrol, menthol, eugenol, cinnamaldehyde, or anycomponent containing them separately or mixed as well as the isomers,derivatives and mixtures thereof. These agents are interspersed inedible clays selected from stevensite, bentonite, kaolinite, smectite,illite, chlorite, montmorillonite, laponite, beidellite, nontronite,saponite, sauconite, hectorite, halloysite, vermiculite, or sepiolite ortheir either natural or caused interlayered mixtures.

Said volatile antimicrobial agent is present in said composition in aweight ratio ranging from 0.005 to 0.33 compared to said edible clay.

The method for manufacturing said composition comprises the followingsteps:

i. Said volatile antimicrobial agent is put into solution in an organicor mineral solvent in order to obtain the antimicrobial solution.

ii. Said thereby obtained antimicrobial solution is mixed with saidedible clay as a powder or pellets under stirring and temperatureconditions giving the possibility of obtaining a homogeneous and stablecomposition formed by a molecular complex containing said edible clayinterspersed by said volatile antimicrobial agent.

In a particular embodiment, this manufacturing method may be detailed asfollows:

-   -   An amount of volatile antimicrobial agent is gradually put into        solution in an amount of vegetable or mineral oil, representing        1 to 20% of the amount of volatile antimicrobial agent, stirred        and heated to a temperature ranging from 30 to 80° C. in order        to obtain a homogeneous and limpid liquid solution, a so-called        antimicrobial solution.    -   An amount of the antimicrobial solution is gradually included by        mixing in an amount of said powdered edible clay, representing        at least three times the amount of antimicrobial solution, in        order to obtain a sievable powder.    -   The obtained sievable powder is calibrated by sieving in order        to obtain the desired grain size.

In a particular embodiment, the volatile antimicrobial agent may bethymol alone or mixed with one or several other volatile antimicrobialagents such as cresol, eugenol, carvacrol, cineol, menthol orcinnamaldehyde or any essential oil containing them separately or mixedand the edible clay may be stevensite or bentonite or their mixture orthe mixture of substances containing them.

In a preferred embodiment, the preparations as detailed above will beintended to be diluted in the cattle feed for administration to ananimal. This dilution may be carried out in a ratio ranging from 50grams of preparation per metric ton of feed to 10 kilograms ofpreparation per metric ton of feed.

In a further preferred embodiment, said preparation, before dilution inthe feed, may contain the volatile antimicrobial agent at a weight ratioranging from 0.1 to 0.33 compared to the edible clay, preferentially ina weight ratio from 0.15 to 0.2 compared to clay.

One object of the present invention is the use of said compositions as afeed additive for animals added to the feed and taken via an oral route.

In every case, the use of said compositions as feed additives areintended to exert a multitude of actions emanating from the propertiesof the substances which they contain, i.e.:

-   -   the growth promoting activity due to the antiseptic properties        of the volatile antiseptic agents capable of reducing pathogenic        or commensal intestinal flora.    -   the antiparasitic, anticoccidian and antihistomoniasis activity        in particular due to the antiparasitic activity of the volatile        antimicrobial agents.    -   the antifungal activity due to the antifungal activity of the        volatile antimicrobial agents giving the possibility of        inhibiting the fungi responsible for production of mycotoxins.    -   the mycotoxin adsorption activity due to the chelating        properties of clays.    -   the cholagogue activity due to the pharmacological properties of        the volatile antimicrobial agents.    -   the immunostimulating activity due to the pharmacological        properties of the volatile antimicrobial agents.    -   the protective intestinal activity due both to the intestinal        bandage properties of clay and to the antiseptic intestinal        properties of the volatile antimicrobial agents.

In every case, the use of said compositions as feed additives intendedto exert a multitude of favorable actions on the animal body has theconsequence of preserving intestinal, hepatobiliary and immune integritywith positive repercussions on preserving the general health of theanimals receiving said compositions as feed additives.

The examples which follow are intended to illustrate certain aspects ofthe invention without, however, being limiting.

On the one hand, the inventor proceeded with experiments with differenttypes of volatile antimicrobial agents and different types of clays. Theresults gave the possibility of showing a displacement of thediffraction x-ray peaks of the characteristic molecules of the claystested, i.e. stevensite and bentonite in a direction which shows anincrease in the interfoliar distance of interspersed clays by volatileantimicrobial agents as compared with clays before interspersion. Thisjustifies and explains the perfectly stable bond of the volatileantimicrobial agents on the clays when they are mixed according to themethod, object of the invention. On the other hand, the inventor testedthe efficiency of the composition with particularly effective doses andratios of the composition under in vitro and in vivo conditions:

EXAMPLE 1 X-Ray Diffraction Test

Preparations of a final weight of 1,000 grams were made with 150 gramsof thymol put into solution according to the method of the inventionwith 20 milliliters of table oil at a temperature of 60° C. The therebyobtained antiseptic solution was mixed with 830 grams of Moroccanghassoul or with 830 grams of Moroccan bentonite or with 830 grams of a50%/50% ghassoul/bentonite mixture (preparation a).

Control compositions were prepared:

Preparation b/ The same pure clays without any additive.

Preparation c/ The same clays with 20 ml of table oil alone.

Preparation d/ The same clays with thymol alone as a crystallizedpowder.

Preparation e/ The same clays with liquefied thymol by heating to 60° C.without any vegetable oil.

The preparations a, b and c were subject to an x-ray diffraction testaccording to the usual standards for treating clays in this analyticalmethod.

The obtained results show a displacement of the specific peak ofbentonite and of stevensite in the spectrum, in a surprising way in thecase of the preparations according to the method of the invention(preparation a) as compared with the control of pure clays (preparationb) and of clays having been mixed with table oil alone (preparation c)(results in Table 1). At the same time, the results show that for thepreparation (d) containing thymol as a crystallized powder mixed withclay, the obtained powder is heterogeneous and the obtained x-raydiffraction spectrum was not able to be utilized. For the preparation(e) in which thymol was liquified by heating and mixed with clay withoutany vegetable oil, it is seen that thymol recrystallizes and forms hardlumps. The thereby obtained mixture is heterogeneous and cannot meet thecriteria for which the invention was elaborated.

This shows on the one hand that the manufacturing method used in theinvention actually gives the possibility of ending up with interspersionof thymol in the interfoliar space of the clays, which leads to a stableand homogeneous dispersion of thymol in clay and to an increase in thedistance of the interfoliar space of the clays therefore improvinghydrophobicity and the capability of the clays of adsorbing the toxins.

These results show on the other hand that the mixtures with thymol andclay by obvious methods using crystallized thymol or liquified thymol byheating do not end up with the result expected by the invention.

TABLE 1 Interfoliar distance of the clays according to the preparationmodes a, b and c. Bentonite Stevensite With With With table oil and Withtable oil and Crude table oil essential oil Crude table oil essentialoil Clays (prep. b) (prep.c) (prep. a) (prep. b) (prep. c) (prep. a)Distance 15.23 15.23 15.69 15.75 16.15 16.51 between sheets (inangstroms)

EXAMPLE 2 In Vivo Test

Batches of 25 young broilers as well as 12 turkey poults were fed with afeed containing the preparation of the invention in an amount of 100grams, 500 grams, 1 kilogram or 2 kilograms per metric ton of feed.Control batches of the same size were fed with a feed not containing anyantibiotic or antiparasitic agent. Other control batches of the samesize were fed with a feed containing Flavomycin in an amount of 200grams per metric ton of feed and Salinomycin in an amount of 70 gramsper metric ton of feed for the broilers and 100 grams per metric ton ofmonensin for the turkey poults. During five weeks of treatment, fecessamples of each subject in each batch were analyzed by microscopy and bysuitable microbiological analysis for evaluating the number of bacteria,of yeast, of fungi and of oocytes of protozoa in particular of thespecies Eimeria. sp involved in coccidiosis in chicken and turkeys. Atthe end of the five weeks of the experiment, the subjects weresacrificed and an autopsy was carried out by professional veterinaries,specialists in avian pathology. The goal of the autopsy was to evaluatethe lesional scores at the intestine and the integrity condition of theliver, of the kidneys, of the lungs and of the spleen and of theintestine.

The obtained results show highly significant reductions in the number ofbacteria, of yeasts, of fungi and oocytes in the batches having receivedthe preparation of the invention in their feed at doses of 1 kilogramper metric ton and 2 kilograms per metric ton as compared with controlbatches having received a neutral feed. The batches having received thepreparation of the invention in the feed at doses of 100 grams and 500grams per metric ton of feed did not have any significant difference ascompared with the control. The batches having received the antibioticand the antiparasitic agent in the feed have a visible butnon-significant reduction as compared with the control. However, thenumber of bacteria, of yeasts, of fungi and oocytes in batches havingreceived the preparation of the invention at the doses of 1 kilogram and2 kilograms per metric ton of feed is significantly less than the numberof bacteria, yeasts, fungi and oocytes recorded in the batches havingreceived the antibiotic and the antiparasitic agent in the feed. Theseresults show that the preparation according to the invention used as anadditive in chicken and turkey feed has multiple activities likepromoting growth (reduction in the intestinal flora), as anantiparasitic (anticoccidian) agent and an antifungal agentsignificantly superior to the antibiotics and antiparasitic agents usedin this test. The results of the autopsy also show that the intestinallesion, kidney, lung, spleen and liver congestion scores aresignificantly lower in the batches having received the feed containingthe preparation of the invention as compared with the patches havingreceived the neutral feed or the feed containing the antibiotic and theantiparasitic agent. These results again show that the preparation ofthe invention used as an additive in chicken and turkey feed hasactivities protecting intestinal integrity, hepatobiliary protectiveactivities, activities purifying the lungs and kidneys and protectingthe spleen. These results confirm that the preparation of the inventionrepresents a solution with multiple activities for combating pathologiesof chicken and of turkeys which are multifactorial diseases.

Batches of 25 chicks of one day of age were fed for 5 weeks on averagewith respectively:

-   -   batch 1: a white “broiler” feed which contains neither        antibiotics nor antiparasitic agents;    -   batch 2: a feed containing a growth factor antibiotic        “Flavomycin” in an amount of 200 milligrams per kilogram of feed        and an antiparasitic agent “Salynomycin” in an amount of 70        milligrams per kilogram;    -   batch 3: a feed containing the preparation of the invention in        the feed at a proportion of 100 grams per metric ton of feed;    -   batch 4: a feed containing the preparation of the invention in        the feed at a proportion of 500 grams per metric ton of feed;    -   batch 5: a feed containing the preparation of the invention in        the feed at a proportion of 1 kg per metric ton of feed;    -   batch 6: a feed containing the preparation of the invention in        the feed at a proportion of 2 kg per metric ton of feed;

TABLE 2 Zootechnical and microbiological results of the broiler in vivotest Con- Mor- sump- Body Bacterial load Fungal load tality tion weight(CFU/g of (CFU/g of rate index (g) faeces) faeces Batch 1 0% 2.3 105 ±8.6  1 · 10¹⁰ ± 0.3 8.6 · 10⁹ ± 3.7 Batch 2 0% 2.2 110 ± 6.4 4.9 · 10⁹ ±2.1 1.6 · 10⁹ ± 0.3 Batch 3 0% 2.2 113 ± 3.4 4.5 · 10⁹ ± 3.2 5.7 · 10⁸ ±1.2 Batch 4 0% 2.1 121 ± 4.5 3.2 · 10⁸ ± 4.1 1.3 · 10⁸ ± 0.3 Batch 5 0%1.9 138 ± 6.6 7.3 · 10⁷ ± 5.2 8.6 · 10⁷ ± 1.5 Batch 6 0% 1.8 157 ± 2.2  2 · 10⁷ ± 1.70  5 · 10⁷ ± 1.1

The in vivo test for turkeys gave similar results to those obtained inthe broiler chicken in vivo test.

EXAMPLE 3 Field Tests

Field tests were carried out in a farm raising chicken broilers and afarm raising turkey broilers. In these tests, two batches of 13,500chicks each received the preparation of the invention at the dose of twokilograms per metric ton of feed during the whole duration of the tape(40 days for chicken and 13 weeks for turkeys). Two other batches of13,500 chicks each received the preparation of the invention at the doseof 1 kilogram per metric ton of feed and two other batches of 13,500chicks each received a feed containing the antibiotic Flavomycin at 200grams per metric ton of feed and the antiparasitic agent Salynomycin at70 grams per metric ton of feed for chicken and monensin for turkeys. Atthe end of the strip, the zootechnical performances and the lesionscores were measured for each batch.

The Results Show:

Mortality: the percentage of dead chicken and turkeys during the raisingcycle was 2.9% for chicken and 2.5% for turkeys at the batches havingreceived 1 kilogram or 2 kilograms of preparation of the invention permetric ton of feed. At the batches having received the antibiotic andthe antiparasitic agent in the feed, the mortality was 5.2% for turkeysand 5.9% for chicken.

Average weight: The average weight of both batches having received 1kilogram or 2 kilograms per metric ton of feed of the preparation of theinvention is 2.3 kg per subject sold in chicken and 12.8 kg in turkeys,the one of the two batches having received the antibiotic and theantiparasitic agent was 2.135 kg in chicken and 11.9 kg in turkeys.

Consumption index: for the batches having received two kilograms of thepreparation of the invention per metric ton of feed was 1.68, that ofthe batches having received one kilogram of the preparation per metricton of feed was 1.82, the one of the two batches having received theantibiotic and the antiparasitic agent was of the order of 1.98.

The titers of the antibodies related to the vaccines used: theinhibition titer of hemagglutination as compared with the antibodies ofthe viruses of Newcastle's disease: the batches having received thepreparation in an amount of two kilograms and one kilogram per metricton of feed was 64, 64, 64, 32 respectively and for the two batcheshaving received the antibiotic and the anti-coccidian agent, they were16 and 16.

The lesional score of the intestine: The lesional scores of theintestine were lowest (1.22) for the batches having received thepreparation of the invention in an amount of 2 kg and 1 kg while thescores for the batches having received the antibiotic and theanti-coccidian agent were of the order of 2.74 and 3.13.

The score of the integrity of the organs: the aspect of the organs(liver, spleen, lungs, muscles and bones) were clearly more healthy (notshowing any sign of congestion) for the batches having received thepreparation of the invention in an amount of 2 kg and 1 kg per metricton of feed while congestion signs visible to the naked eye wereascertained in the majority of the autopsied in both batches havingreceived the antibiotic and the antiparasitic agent.

These results surprisingly show that the preparation of the inventionexerts the multiple activities for which it was designed and this evenunder intensive raising conditions in the field.

EXAMPLE 4 Inhibition and Adsorption of Mycotoxins in the Feed and theCorn

Samples of corn and of composed feed were treated with variable amountsof the preparation of the invention in the proportions of 2 kg, 4 kg and6 kg per metric ton of feed. These samples were hermetically packagedand incubated at a temperature of 27.5° C. 50 gram aliquots were takenafter four weeks for dosage of the mycotoxins: the results show that thecorn samples having been treated by the preparation of the invention hada significantly lower level of DON (deoxynivalenol), of ZON(Zearalenone) and of ochratoxin than the control sample. This inhibitionand adsorption effect on mycotoxins is increasing according to the doseused of the preparation of the invention. A similar result was obtainedfor the composed feed sample treated by the preparation of the inventionwith respect to the untreated sample and this for the mycotoxins,ochratoxin (ZON) and aflatoxin.

These results show that the preparation of the invention also has thecapability of protecting the feed and the corn from mycotoxins whichrepresent a significant risk factor promoting the outbreak of diseasesand causing in acute cases, mortal intoxications of the animals.

TABLE 3 Percentage of reduction of the mycotoxins in corn treated withthe preparation of the invention as compared with the untreated control.Preparation 0.2 g/100 0.4 g/100 0.6 g/100 Mycotoxins g of corn g of corng of corn Zearalenone 56% 59% 61% DON 63% 73% 75% ochratoxin 13% 22% 27%

TABLE 4 Reduction percentage of the mycotoxins in the treated composedfeed with respect to the untreated control. Preparation 0.2 g/100 0.4g/100 0.6 g/100 Mycotoxins g of feed g of feed g of feed Zearalenone  35% 63% 94% Aflatoxin 74.35% 86% 89%

1-37. (canceled)
 38. A composition combining both antimicrobial andtoxin-adsorption activities, characterized in that it is formed by amolecular complex comprising an edible clay interspersed by a volatileantimicrobial agent.
 39. The composition according to claim 38,characterized in that said volatile antimicrobial agent is an antisepticaromatic alcohol selected from thymol, cresol, carvacrol, eugenol,menthol, cinnamaldehyde or mixtures or isomers thereof.
 40. Thecomposition according to claim 38, characterized in that said volatileantimicrobial agent is formed by a mixture of two or more natural orsynthetic antimicrobial agents.
 41. The composition according to claim38, characterized in that said edible clay is selected from stevensite,bentonite, kaolinite, smectite, illite, chlorite, montmorillonite,laponite, beidellite, nontronite, saponite, sauconite, hectorite,halloysite, vermiculite, or sepiolite or their either caused or naturalinterlayered mixtures.
 42. The composition according to claim 38,characterized in that said edible clay is a mixture of Ghassoul fromMorocco and bentonite from Morocco.
 43. The composition according toclaim 42, characterized in that said mixture of Ghassoul and bentonitefrom Morocco consists of at least 5% by weight Ghassoul from Morocco.44. The composition according to claim 38, characterized in that saidvolatile antimicrobial agent is present in a mass ratio from 0.005 to0.33 based on said edible clay.
 45. A method for manufacturing acomposition comprising an edible clay and a volatile antimicrobial agentcomprising: i) adding said volatile antimicrobial agent into solutionwith an organic or mineral solvent in order to obtain an antimicrobialsolution; and ii) mixing said antimicrobial solution with said edibleclay as a powder or pellets under stirring and temperature conditions toobtain a homogenous and stable composition formed by a molecular complexcontaining said edible clay interspersed by said volatile antimicrobialagent.
 46. The manufacturing method according to claim 45, characterizedin that said volatile antimicrobial agent is selected from thymol,cresol, carvacrol, menthol, eugenol, cinnamaldehyde, or mixtures orisomers thereof, said organic or mineral solvent is a vegetable oil andsaid edible clay is selected from stevensite, bentonite, kaolinite,smectite, illite, chlorite, montmorillonite, laponite, beidellite,nontronite, saponite, sauconite, hectorite, halloysite, vermiculite, orsepiolite or their caused or natural interlayered mixtures.
 47. Themanufacturing method according to claim 45 wherein: crystallized thymolis gradually put into solution in a volume of vegetable oil heated to atemperature allowing it to melt so as to obtain a homogeneous and limpidliquid composition (an antimicrobial solution); mixing saidantimicrobial solution with an amount of said edible clay as a powdercapable of absorbing it in order to obtain a molecular complex as ahomogenous and stable powder; and subjecting said powder to acalibration or sieving operation to obtain the desired grain size. 48.The manufacturing method according to claim 45, characterized in thatthe volatile antimicrobial agent is a mixture of thymol and cresol. 49.The manufacturing method according to claim 45, characterized in thatthe volatile antimicrobial agent is a mixture of thymol, cresol andmenthol.
 50. A method of reducing or suppressing the development ofpathogenic or toxinogenic germs in an animal comprising administering acomposition according to claim 38 to an animal or its surroundings. 51.The method according to claim 50, wherein said composition isadministered to said animal in a feed containing said composition. 52.The method according to claim 50, wherein said composition is added tofeed, drinking water, litter, walls of the animal enclosure, barn area,rearing equipment or the vehicles transporting the animal.
 53. Themethod according to claim 50, wherein said animal is a mammal, fish, beeor poultry.
 54. The method according to claim 53, wherein said mammal isa bovine animal, ovine animal, rabbit, pig, caprine animal or equineanimal.
 55. The method according to claim 53, wherein said poultry areselected from chicken broilers, laying hens, breeding roosters and hens,guinea fowl, turkeys, quail, ducks, geese and pigeons.
 56. The methodaccording to claim 50, said method reducing or suppressing developmentof bacteria, fungi, parasites, bacteriotoxins and mycotoxins in theanimal.